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LAPTM4B基因多态性与胃癌易感性的关系。

Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer.

作者信息

Liu Y, Zhang Q-Y, Qian N, Zhou R-L

机构信息

The Medical School of Da Tong University, Shanxi Medical University, Taiyuan, China.

出版信息

Ann Oncol. 2007 Feb;18(2):311-6. doi: 10.1093/annonc/mdl394. Epub 2006 Oct 30.

Abstract

BACKGROUND

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4beta) was mapped to 8q22, and contains seven exons. The 2.25-kb messenger RNA of the gene encodes a putative lysosome-associated protein with four transmembrane regions. There are two alleles of the gene, named as LAPTM4B1 and LAPTM4B2. Allele *1 differs from allele *2 in that it contains only one copy of a 19-bp sequence in the 5' untranslated region (UTR), whereas this sequence is duplicated and tandemly arranged in allele *2. Studies showed that the allelic variation of LAPTM4B was associated with the genetic susceptibility of hepatocellular carcinoma but not with that of esophageal squamous cell carcinoma. This study was designed to investigate the possible association between the allelic variation of LAPTM4B and the genetic susceptibility of gastric cancer.

MATERIALS AND METHODS

The genotype of LAPTM4B was analyzed in 350 unrelated healthy adult individuals and 214 patients with gastric cancer by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B was analyzed by chi(2) test.

RESULTS

The allelic frequencies of the *2 were 33.88% and 24.14% in the gastric cancer group and the healthy control group, respectively, which was significantly different between the two groups (P < 0.001). There was a significant difference in the overall genotypic distribution between the patients and the controls (P = 0.023). The risk of suffering from gastric cancer was increased 1.819 times in the individuals of the *1/2 genotype [95% confidence interval (CI) 1.273-2.601] and 2.387 times in the individuals of the *2/2 genotype of LAPTM4B (95% CI 1.195-4.767) compared with the *1/1 genotype. No association between the genotypic distribution of LAPTM4B and the clinical information on patients of gastric cancer such as age, pathological type, differentiation classification of TNM, and infection of hepatitis B virus was shown.

CONCLUSION

This study indicated that allele *2 of LAPTM4B might be the risk factor of gastric cancer, which could be associated with genetic susceptibility of gastric cancer.

摘要

背景

一种名为LAPTM4B(溶酶体相关蛋白跨膜4β)的新基因被定位到8q22,包含7个外显子。该基因2.25kb的信使核糖核酸编码一种具有四个跨膜区的假定溶酶体相关蛋白。该基因有两个等位基因,命名为LAPTM4B1和LAPTM4B2。等位基因1与等位基因2的不同之处在于,它在5'非翻译区(UTR)仅包含一个19bp序列的拷贝,而该序列在等位基因*2中是重复且串联排列的。研究表明,LAPTM4B的等位基因变异与肝细胞癌的遗传易感性相关,但与食管鳞状细胞癌无关。本研究旨在探讨LAPTM4B的等位基因变异与胃癌遗传易感性之间可能存在的关联。

材料与方法

利用基于特异性引物的聚合酶链反应,对350名无亲缘关系的健康成年个体和214例胃癌患者进行LAPTM4B基因型分析。采用卡方检验分析LAPTM4B的基因型分布。

结果

2等位基因频率在胃癌组和健康对照组中分别为33.88%和24.14%,两组间差异有统计学意义(P<0.001)。患者与对照组的总体基因型分布存在显著差异(P=0.023)。与1/1基因型相比,LAPTM4B基因*1/2基因型个体患胃癌的风险增加1.819倍[95%置信区间(CI)1.273 - 2.601],*2/2基因型个体患胃癌的风险增加2.387倍(95%CI 1.195 - 4.767)。未显示LAPTM4B的基因型分布与胃癌患者的年龄、病理类型、TNM分化分级和乙型肝炎病毒感染等临床信息之间存在关联。

结论

本研究表明,LAPTM4B基因的*2等位基因可能是胃癌的危险因素,可能与胃癌的遗传易感性相关。

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